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S P Brennecke

Publications and source records attributed to S P Brennecke.

At least 19 recordsLinked to original sources
PubMed2006

Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach.

Pre-eclampsia/eclampsia (PE/E) is a common and serious disorder of human pregnancy that is associated with substantial maternal and perinatal morbidity and mortality. The suspected aetiology of PE/E is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. By assuming that the underlying liability towards PE/E susceptibility is inherently quantitative, any PE/E susceptibility gene would represent a quantitative trait locus (QTL). This assumption enables a more refined and powerful variance components procedure using a threshold model for our PE/E statistical analysis. Using this more efficient linkage approach, we have now re-analysed our previously completed Australian/New Zealand genome scan data to identify two novel PE/E susceptibility QTLs on chromosomes 5q and 13q. We have obtained strong evidence of linkage on 5q with a peak logarithm-of-odds (LOD) score of 3.12 between D5S644 and D5S433 [at approximately 121 centimorgan (cM)] and strong evidence of linkage on 13q with a peak LOD score of 3.10 between D13S1265 and D13S173 (at approximately 123 cM). Objective identification and prioritization of positional candidate genes using the quantitative bioinformatics program GeneSniffer revealed highly plausible PE/E candidate genes encoding aminopeptidase enzymes and a placental peptide hormone on the 5q QTL and two type IV collagens on the 13q QTL regions, respectively.

Analysis of Variance↗
PubMed2006

Homeobox gene DLX4 expression is increased in idiopathic human fetal growth restriction.

Idiopathic fetal growth restriction (FGR) is often associated with placental insufficiency. Previously, we isolated and characterized homeobox gene DLX4 from the placenta and provided evidence that DLX4 may regulate placental development. Here, we have investigated whether DLX4 expression levels were altered in idiopathic FGR. FGR-affected placentae were collected based on strict clinical criteria. DLX4 mRNA expression was analysed in placentae obtained from pregnancies complicated by idiopathic FGR and gestation-matched control pregnancies (n = 25 each). Initial RT-PCR results showed a qualitative increase in DLX4 mRNA in both FGR-affected placentae and gestation-matched controls. Real-time PCR showed a 3-fold increase in DLX4 mRNA levels in FGR-affected placentae compared with gestation-matched controls (P < 0.005). Western immunoblotting using a rabbit DLX4 polyclonal antibody revealed significantly increased levels of DLX4 protein in term FGR-affected placentae compared with term controls [5500.1 +/- 21.8 (n = 10) versus 3533.2 +/- 22.4 (n = 10); P < 0.001]. Qualitative immunohistochemical analyses of term placentae showed moderately increased immunoreactivity for DLX4 antigen in the FGR-affected placentae in syncytiotrophoblasts, residual cytotrophoblast cells and endothelial cells of the fetal capillaries compared with gestation-matched control term placentae. We conclude that the increased expression of homeobox gene DLX4 may be a contributing factor to the developmental abnormalities seen in the FGR-affected placentae.

Adult↗
PubMed2006

Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22.

Pre-eclampsia/eclampsia (PE/E) is a common, serious medical disorder of human pregnancy. Familial association of PE/E has been recognized for decades, but the genetics are complex and poorly understood. In an attempt to identify PE/E susceptibility genes, we embarked on a positional cloning strategy using 34 Australian and New Zealand PE/E pedigrees. An initial 10-cM resolution genome scan revealed a putative susceptibility locus spanning a broad region on chromosome 2 that overlaps an independently determined linkage signal seen in Icelandic PE pedigrees. Subsequent fine mapping using 25 additional short tandem repeat (STR) markers in this region and non-parametric multipoint linkage analysis did not change the overall position. Under a strict diagnosis of PE, we obtained significant evidence of linkage on 2q with a peak log-of-odds ratio score (LOD) of 3.43 near marker D2S151 at 155 cM. To prioritize positional candidate genes at the 2q locus for detailed analysis, we applied an objective prioritization strategy that integrates quantitative bioinformatics, assessment of differential gene expression and association analysis of single-nucleotide polymorphisms (SNPs). Highest priority was assigned to the activin receptor gene ACVR2. This gene also showed >10-fold differential gene expression in human decidual tissue from normotensive and PE individuals. We genotyped five known SNPs in this gene in our pedigrees and performed tests for association and linkage disequilibrium. One SNP (rs1424954) showed strong preliminary evidence of association with PE (P = 0.007), whereas two others (rs1364658 and rs1895694) exhibited nominal evidence (P < 0.05). Haplotype analysis revealed no additional association information. There was evidence of weak linkage disequilibrium among these SNPs. The highest observed LD occurred between the two strongest associated SNPs, suggesting that the observed signals may be the signature of an observed functional variant.

Activin Receptors, Type II↗
PubMed2006

Homeobox genes are differentially expressed in macrovascular human umbilical vein endothelial cells and microvascular placental endothelial cells.

Angiogenesis is fundamental to normal placental development. Aberrant angiogenesis within the placental terminal villi is a characteristic of significant placental pathologies and includes structural and vascular abnormalities as well as altered endothelial cell function, which substantially impacts on maternal-fetal exchange. Homeobox gene transcription factors regulate vascular development in embryonic and adult tissues, but their role in the placental microvasculature is not well known. In this study, we isolated and enriched human placental microvascular endothelial cells (PLEC) by a perfusion-based method and compared homeobox gene expression between PLEC and macrovascular human umbilical vein endothelial cells (HUVEC). Reverse transcriptase PCR detected mRNA expression of homeobox genes DLX3, DLX4, MSX2, GAX and HLX1 in both PLEC and HUVEC. DLX4 and HLX1 have not been previously detected in PLEC and with the exception of GAX, none of these homeobox genes have been previously identified in HUVEC. There was lower expression of HLX1 mRNA in HUVEC compared with PLEC. Using real-time PCR analysis PLEC HLX1 mRNA expression relative to housekeeping gene GAPDH was 0.9+/-0.06 fold of the calibrator (n=6) versus 0.2+/-0.06 (n=6) for HUVEC, p<0.001. These data provided evidence of heterogeneity in homeobox gene expression between microvascular PLEC and macrovascular HUVEC that most likely reflects significant differences in endothelial cell function in the two different cellular environments.

Endothelial Cells↗
PubMed2006

Increased adrenomedullin protein content and mRNA expression in human fetal membranes but not placental tissue in pre-eclampsia.

The relationship between Pre-eclampsia (PE) and placental production of Adrenomedullin (AdM) is not completely understood. This study measured placental and fetal membrane AdM protein concentrations by specific radioimmunoassay and mRNA expression by Northern blot analysis in samples obtained at either term or preterm gestation from women either in labour or not in labour. Samples were obtained from women with normotensive and pre-eclamptic pregnancies. There were significant increases in immunoreactive AdM protein concentration (pg/mg DNA) in choriodecidua and amnion of women with PE compared to normal pregnancy for the preterm not-in-labour group (choriodecidua: control 124 +/- 16, n = 10, PE 361 +/- 35, n = 10; amnion: control 94 +/- 12, n = 10, PE 153 +/- 19, n = 10) and for the term not-in-labour (choriodecidua: control 128 +/- 17, n = 14, PE 459 +/- 51, n = 8; amnion: control 112 +/- 15, n = 14, PE 253 +/- 57, n = 8) and in-labour (choriodecidua: control 531 +/- 74, n = 14, PE 881 +/- 188, n = 8; amnion: control 545 +/- 84, n = 14, PE 1008 +/- 230, n = 8) groups. AdM mRNA relative abundance was greater in preterm, not-in-labour choriodecidual samples in PE, but not in amnion. In addition, this study observed labour-associated increases in choriodecidual and amniotic irAdM in term pre-eclamptic and control patients. However, there were no significant changes in AdM protein or mRNA expressions between any of the groups for placental tissue. These results suggest that fetal membranes, but not placental, production of AdM is increased at the post-translational level during PE in preterm and term tissues and at the pre-translational level during PE in preterm tissues. Fetal membranes, AdM may play an important role in the regulation of feto-placental hemodynamics and fetal physiology during pre-eclampsia.

Adrenomedullin↗
PubMed2006

A cost-effectiveness analysis of the intrapartum fetal pulse oximetry multicentre randomised controlled trial (the FOREMOST trial).

OBJECTIVE: To report an economic analysis of the Australian intrapartum fetal pulse oximetry (FPO) multicentre randomised controlled trial (the FOREMOST trial), which examined whether adding FPO to conventional cardiotocographic (CTG) monitoring (intervention group) was cost-effective in reducing operative delivery rates for non-reassuring fetal status compared with the use of CTG alone (control group). DESIGN: Cost-effectiveness analysis of the FOREMOST trial. SETTING: Four Australian maternity hospitals, each with more than 4000 births/year. POPULATION: Women in labour at > or =36 weeks of gestation, with a non-reassuring CTG. METHODS: Costs were for treatment-related expenses, incorporating diagnosis-related grouping costs and direct costs (including fetal monitoring). Incremental cost-effectiveness ratio (ICER) and cost-effectiveness plane were calculated, and sensitivity analysis was conducted. The primary outcome was that of the clinical trial: operative delivery for non-reassuring fetal status avoided in the intervention group relative to that in the control group. MAIN OUTCOME MEASURES: The ICER. RESULTS: The ICER demonstrated a saving of $A813 for each operative birth for non-reassuring fetal status averted by the addition of FPO to CTG monitoring compared with the use of CTG monitoring alone. CONCLUSION: The addition of FPO to CTG monitoring represented a less costly and more effective use of resources to reduce operative delivery rates for non-reassuring fetal status than the use of conventional CTG monitoring alone.

Adult↗
PubMed2005

Gene expression of the constant region of the heavy chain of immunoglobulin G (IgG CRHC) is down-regulated in human decidua in association with preeclampsia.

An aberrant interaction at the maternal/fetal interface between the genetically distinct fetal trophoblast cells and cells of the maternal decidua has been proposed as an initiating factor in one of the major complications of human pregnancy, preeclampsia. Biochemical and epidemiological studies suggest that the immune system plays an important role in preeclampsia. Thus, the aim of this study was to determine the decidual gene expression status in preeclampsia of one of the key components of the adaptive immune system. Total RNA was extracted from decidua collected from women with normal pregnancies and those complicated by preeclampsia. Reverse Northern analysis was performed on 72 cDNAs from human decidua and differentially expressed genes identified were analysed further using semi-quantitative RT-PCR and Northern blot analysis. Expression of the gene encoding the constant region of the heavy chain of immunoglobulin G (IgG CRHC) was shown to be down-regulated in association with preeclampsia. These data support the hypothesis that immune maladaptation may play an important role in the pathogenesis of preeclampsia.

Decidua↗
PubMed2005

Fetal growth restriction is associated with increased apoptosis in the chorionic trophoblast cells of human fetal membranes.

The aim of the study was to determine the incidence and spatial distribution of apoptotic cell in fetal membranes obtained from human pregnancies complicated with fetal growth restriction (FGR) for which there was no established cause. Fetal membrane samples from normal (n=10) and FGR-affected (n=10) pregnancies were collected and stored following delivery. The incidence of apoptosis and the number of apoptotic cells in normal and FGR-affected fetal membranes were determined using immunohistochemistry and a monoclonal antibody for neo-epitope of cytokeratin-18, M30. The level of apoptotic proteins in FGR-fetal membranes compared to the normal tissue was determined using Western immunoblotting analysis. Multiple labeling of trophoblast cells using immunofluorescence markers was used to investigate regional differences in localization of apoptotic cells between normal and FGR-affected fetal membranes. Apoptosis was detected in both normal and FGR-affected fetal membranes. However, quantitative analysis of apoptotic cells by immunohistochemistry showed a significant increase in FGR-affected fetal membranes compared to normal (p<0.005). Furthermore, it was observed that apoptotic cells were predominantly localized to chorio-decidual layer of the fetal membrane. By using semi-quantitative analysis of Western immunoblotting, a significant increase in the levels of the apoptotic marker proteins poly-ribo (ADP) polymerase (PARP) and the neo-epitope of cytokeratin-18 were observed in FGR-affected fetal membranes compared to normal (p<0.005). Immunofluorescence studies further confirmed the restriction of the apoptotic cells to the chorionic trophoblast cells in FGR-affected fetal membranes. Our results document for the first time an increased incidence of apoptosis in FGR-affected fetal membranes, with the apoptotic cells restricted primarily to the chorionic trophoblast layer of the fetal membranes. Increased apoptosis in FGR-affected fetal membranes may impair functions of the fetal membranes that are important for normal fetal development and growth. Elucidation of the molecular mechanisms involved in the control of apoptosis in the chorionic trophoblast layer in the FGR-affected fetal membranes may provide further insights into the etiology of FGR.

Apoptosis↗
PubMed2005

Detection of CAG repeats in pre-eclampsia/eclampsia using the repeat expansion detection method.

Pre-eclampsia/eclampsia is a serious disorder of human pregnancy that has a worldwide incidence of 2-10% and carries a severe morbidity and mortality risk for both mother and child. Its precise cause remains unknown. However, there is increasing evidence of an underlying complex maternal genetic susceptibility. Its high population incidence in the face of strong negative selection pressure suggests that the gene(s) involved have a selective advantage and/or a high mutation rate. One class of genetic diseases that involve a high mutation rate are the trinucleotide repeat expansion diseases. Thus, the aim of this study was to determine whether there is an association between a trinucleotide (CAG) repeat expansion and pre-eclampsia/eclampsia. We have used the repeat expansion detection (RED) method, which was developed to directly identify clinically significant repeat expansions, to analyse genomic DNA from an Australian and New Zealand population. The maximal CAG repeat length for each individual was recorded and the Mann-Whitney U and Wilcoxon rank sum test for independent samples were used to compare distributions for CAG/CTG repeats between two populations. There were no statistically significant differences between the distribution of CAG repeats in normotensive (n = 59) and severe pre-eclampsia (n = 69) (Mann-Whitney U = 1732; P = 0.14), and normotensive (n = 59) and eclamptic (n = 15) populations (Mann-Whitney U = 417, P = 0.726). Therefore, these RED results do not support a role for a large CAG expansion in pre-eclampsia/eclampsia. However, these data do not preclude the possibility that a small CAG expansion is associated with the disorder nor do they negate the hypothesis that a highly mutable gene contributes to the genetic component of pre-eclampsia/eclampsia.

Autoradiography↗
PubMed2004

Fine mapping and SNP analysis of positional candidates at the preeclampsia susceptibility locus (PREG1) on chromosome 2.

Genome scans in Icelandic, Australian and New Zealand, and Finnish families have localized putative susceptibility loci for preeclampsia/ eclampsia to chromosome 2. The locus mapped in the Australian and New Zealand study (designated PREG1) was thought to be the same locus as that identified in the Icelandic study. In both these studies, two distinct quantitative trait locus (QTL) regions were evident on chromosome 2. Here, we describe our fine mapping of the PREG1 locus and a genetic analysis of two positional candidate genes. Twenty-five additional microsatellite markers were genotyped within the 74-cM linkage region defined by the combined Icelandic and Australian and New Zealand genome scans. The overall position and shape of the localization evidence obtained using nonparametric multipoint analysis did not change from that seen previously in our 10-cM resolution genome scan; two peaks were displayed, one on chromosome 2p at marker D2S388 (107.46 cM) and the other on chromosome 2q at 151.5 cM at marker D2S2313. Using the robust two-point linkage analysis implemented in the Analyze program, all 25 markers gave positive LOD scores with significant evidence of linkage being seen at marker D2S2313 (151.5 cM), achieving a LOD score of 3.37 under a strict diagnostic model. Suggestive evidence of linkage was seen at marker D2S388 (107.46 cM) with a LOD score of 2.22 under the general diagnostic model. Two candidate genes beneath the peak on chromosome 2p were selected for further analysis using public single nucleotide polymorphisms (SNPs) within these genes. Maximum LOD scores were obtained for an SNP in TACR1 (LOD = 3.5) and for an SNP in TCF7L1 (LOD = 3.33), both achieving genome-wide significance. However, no evidence of association was seen with any of the markers tested. These data strongly support the presence of a susceptibility gene on chromosome 2p11-12 and substantiate the possibility of a second locus on chromosome 2q23.

Australia↗
PubMed2003

Labour-associated changes in adrenomedullin content in human placenta and fetal membranes.

The aim of the present study was to determine the effects of labour and mode of delivery on human placental and fetal membrane content of adrenomedullin (AdM). Placentas and fetal membranes were collected either at term or pre-term gestation from women either in labour or not in labour, and AdM was measured in tissue extracts by specific RIA. There were significant increases in AdM concentrations in amnion and choriodecidua for the in-labour group compared with the not-in-labour group for both pre-term and term gestations. There was no difference in AdM concentration in placental tissue between labour groups. This study provides evidence that fetal membrane AdM is increased in amniotic and choriodecidual tissues in response to labour, and suggests that it may play a role during human labour.

Adrenomedullin↗
PubMed2001

Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients.

AIMS/HYPOTHESIS: We have previously shown that placentae from patients with gestational diabetes mellitus who did not receive insulin had lower glucose transport and utilisation than non-diabetic control subjects. To assess the placental glucose handling characteristics of women with gestational diabetes mellitus receiving insulin, we examined glucose transport and utilisation in placentae from three groups of women after term delivery: those with gestational diabetes mellitus and receiving insulin (n = 9, insulin group); those with gestational diabetes mellitus and not receiving insulin (n = 10, no insulin group); and those with normal, non-diabetic pregnancies (n = 9, control group). METHODS: Dual perfusion of an isolated placental lobule was done using maternal glucose concentrations of 4, 8, 16 and 24 mmol/l. Glucose and L-lactate concentrations in the maternal and fetal effluents were measured. Direct glucose transfer from the maternal to the fetal effluent was measured using 14C-D-glucose. Mean rates in micromol ming(-1) (wet tissue) at maternal glucose concentration of 8 mmol/l are shown. RESULTS: Glucose uptake from the maternal perfusate (insulin group 0.57, no insulin group 0.30) and net glucose transfer to the fetal effluent (insulin group 0.41, no insulin group 0.20) both increased in the placentae of women receiving insulin compared with the diabetic group not receiving insulin. Both groups of patients had lower placental glucose utilisation than the control group (insulin group 0.16, no insulin group 0.10, control group 0.25). CONCLUSION/INTERPRETATION: These results suggest that materno-fetal glucose transport increases in the placentae of women with gestational diabetes mellitus who receive insulin compared with those women who do not receive insulin.

Adult↗
PubMed2001

Blood pressure in late pregnancy and work outside the home.

OBJECTIVE: To assess maternal blood pressure (BP) responses to working outside the home in late pregnancy, using 24-hour ambulatory BP monitoring. METHODS: Our paired observational study involved 24-hour ambulatory BP monitoring of 100 normotensive women (51 primiparas, 49 multiparas) on work and nonwork days. Mean BP differences were calculated for working, postworking, sleeping, and 24-hour periods on both days. Main outcome measures were BP differences between work and nonwork days and subsequent pregnancy hypertension. Comparisons in BP between work and nonwork days were done with Student paired t test. Comparisons between study subgroups were done with unpaired t test. Potential predictors of change in BP were examined using multiple linear regression. RESULTS: During job time, BP was significantly higher on work days than on nonwork days. The mean increase in BP associated with work was 2.6 mmHg (systolic BP, P <.001), 2.8 mmHg (diastolic BP, P <.001), and 2.9 mmHg (mean arterial BP, P <.001). Those observations were independent of parity. More than 10% of our subjects had increased mean arterial BP of 10 mmHg or more during job time on work days compared with nonwork days. Higher absolute BP levels (regression coefficient 0.21, P =.04) and greater perceived job stress (regression coefficient 1.34, P =.04) correlated positively with BP increases at work. Twelve women developed hypertension. Those women had a larger increase on work days in mean systolic (6.6 mmHg compared with 2.1 mmHg, P =.013), mean diastolic (6.4 mmHg compared with 2.3 mmHg, P =.014), and mean arterial (7.4 mmHg compared with 2.3 mmHg, P =.002) BP compared with normotensive women. The magnitude of BP responses to work was a significant predictor of pregnancy hypertension, independent of absolute BP level. CONCLUSION: Blood pressure increased in women when they worked outside the home. The effect of maternal work is important when treating pregnancy hypertension. Ambulatory BP monitoring makes assessment of maternal BP responses to work a practical clinical option.

Adult↗
PubMed2001

An Australian twin study of the genetic basis of preeclampsia and eclampsia.

OBJECTIVE: We investigated maternal versus fetal genetic causes of preeclampsia and eclampsia by assessing concordance between monozygotic and dizygotic female co-twins, between female partners of male monozygotic and dizygotic twin pairs, and between female twins and partners of their male co-twins in dizygotic opposite-sex pairs. STUDY DESIGN: Two large birth cohorts of volunteer Australian female twin pairs (N = 1504 pairs and N = 858 pairs) were screened and interviewed, and available medical and hospital records were obtained and reviewed where indicated, with diagnoses assigned according to predetermined criteria. RESULTS: With strict diagnostic criteria used for preeclampsia and eclampsia, no concordant female twin pairs were found. Collapsing diagnoses of definite, probable, or possible preeclampsia or eclampsia resulted in very low genetic recurrence risk estimates. CONCLUSION: Results from these two cohorts of female twin pairs do not support clear, solely maternal genetic influences on preeclampsia and eclampsia. Numbers of parous female partners of male twins were too low for conclusions to be drawn regarding paternal transmission.

Adult↗
PubMed2001

C677T methylenetetrahydrofolate reductase polymorphism is not a risk factor for pre-eclampsia/eclampsia among Australian women.

The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism results in reduced MTHFR enzymatic activity. This in turn results in increased levels of homocysteine. It has been suggested that increased levels of homocysteine cause vascular disease, which is known to increase the risk of developing pre-eclampsia (PE) during pregnancy. However, recent studies on Japanese, Italian and American populations have failed to reach agreement on an association between the C677T polymorphism and PE. In this study, 156 cases of eclampsia (E)/PE and 79 normal pregnant control cases from an Australian population were genotyped for this mutation. No significant difference could be found in the incidence of the homozygote mutation or in the allele frequency. We conclude from this study that the C677T mutation in our population is not associated with the development of PE/E.

Australia↗
PubMed2000

A genome scan in families from Australia and New Zealand confirms the presence of a maternal susceptibility locus for pre-eclampsia, on chromosome 2.

Epidemiological studies have shown that genetic factors contribute to the etiology of the common and serious pregnancy-specific disorder pre-eclampsia (PE)/eclampsia (E). Candidate-gene studies have provided evidence (albeit controversial) of linkage to several genes, including angiotensinogen on 1q42-43 and eNOS on 7q36. A recent medium-density genome scan in Icelandic families identified significant linkage to D2S286 (at 94.05 cM) on chromosome 2p12 and suggestive linkage to D2S321 (at 157.5 cM) on chromosome 2q23. In the present article, the authors report the results of a medium-density genome scan in 34 families, representing 121 affected women, from Australia and New Zealand. Multipoint nonparametric linkage analysis, using the GENEHUNTER-PLUS program, showed suggestive evidence of linkage to chromosome 2 (LOD=2.58), at 144.7 cM, between D2S112 and D2S151, and to chromosome 11q23-24, between D11S925 and D11S4151 (LOD=2.02 at 121.3 cM). Given the limited precision of estimates of the map location of disease-predisposing loci for complex traits, the present finding on chromosome 2 is consistent with the finding from the Icelandic study, and it may represent evidence of the same locus segregating in the population from Australia and New Zealand. The authors propose that the PE/E-linked locus on chromosome 2p should be designated the "PREG1" (pre-eclampsia, eclampsia gene 1) locus.

Australia↗
PubMed2000

Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation.

AIMS/HYPOTHESIS: Gestational diabetes is associated with complications for the offspring before, during and after delivery. Poor maternal glucose control, however, is a weak predictor of these complications. Given its position at the interface of the maternal and fetal circulations, the placenta possibly plays a crucial part in protecting the fetus from adverse effects from the maternal diabetic milieu. We hypothesised that gestational diabetes may result in changes in placental function, particularly with respect to the uptake, transfer, and/or utilisation of glucose. We aimed to examine glucose transport and utilisation in intact human placental lobules from women with gestational diabetes and those from normal pregnancies. METHOD: Dual perfusion of an isolated placental lobule was done on placentae from diet treated gestational diabetic (n = 7) and normal pregnant patients (n = 9) using maternal glucose concentrations of 4, 8, 16 and 24 mmol/l in random order over a 4-h experiment. Results were expressed in micromol x min(-1) x g(-1). RESULTS: D-glucose uptake from the maternal circulation (control 0.492 vs gestational diabetes mellitus 0.248, at 8 mmol/l maternal glucose), D-glucose utilisation by the placenta (0.255 vs 0.129), D-glucose transfer to the fetal circulation (direct 0.979 vs 0.402; net transfer 0.269 vs 0.118) and L-lactate maternal release into both the fetal (0.052 vs 0.042) and maternal (0.255 vs 0.129) circulation were significantly reduced during in vitro perfusion of placentae from patients with gestational diabetic pregnancies. Transfer of 3H-L-glucose also significantly reduced in the diabetic group (8.1% vs 2.6%). CONCLUSION/INTERPRETATION: These results suggest that placental transport and metabolism of D-glucose is altered during gestational diabetes.

Adult↗